A T follicular helper cell origin for T regulatory type 1 cells

Chronic antigenic stimulation can trigger the differentiation of antigen-experienced CD4+T cells into T regulatory type 1(TR1)cells,a subset of interleukin-10-producing Treg cells that do not express FOxP3.The identities of the progenitor(s)and transcriptional regulators of this T-cell subset remain unclear.Here,we show that the peptide-major histocompatibility complex class Il(pMHCll)monospecific immunoregulatory T-cell pools that arise in vivo in different genetic backgrounds in response to pMHCll-coated nanoparticles(pMHCll-NPs)are invariably comprised of oligoclonal subpools of T follicular helper(TFH)and TR1 cells with a nearly identical clonotypic composition but different functional properties and transcription factor expression profles.Pseudotime analyses of scRNAseq data and multidimensional mass cytometry revealed progressive downregulation and upregulation of TFH and TR1 markers,respectively.Furthermore,pMHCIl-NPs trigger cognate TR1 cell formation in TFH cell-transfused immunodeficient hosts,and T-cell-specific deletion of Bcl6 or Irf4 blunts both the TFH expansion and TR1 formation induced by pMHCl-NPs.In contrast,deletion of Prdm1 selectively abrogates the TFH-to-TR1 conversion.Bcl6 and Prdm1 are also necessary for anti-CD3 mAbinduced TR1 formation.Thus,TFH cells can differentiate into TR1 cells in vivo,and BLIMP1 is a gatekeeper of this cellular reprogramming event.

Inner-View of Nanomaterial Incited Protein Conformational Changes: Insights into Desig

Nanoparticle bioreactivity critically depends upon interaction between proteins and nanomaterials(NM).Te formation of the“protein corona”(PC)is the efect of such nanoprotein interactions.PC has a wide usage in pharmaceuticals,drug delivery,medicine,and industrial biotechnology.Terefore,a detailed in-vitro,in-vivo,and in-silico understanding of nanoprotein interaction is fundamental and has a genuine contemporary appeal.NM surfaces can modify the protein conformation during interaction,or NMs themselves can lead to self-aggregations.Both phenomena can change the whole downstream bioreactivity of the concerned nanosystem.Te main aim of this review is to understand the mechanistic view of NM-protein interaction and recapitulate the underlying physical chemistry behind the formation of such complicated macromolecular assemblies,to provide a critical overview of the diferent models describing NM induced structural and functional modifcation of proteins.Te review also attempts to point out the current limitation in understanding the feld and highlights the future scopes,involving a plausible proposition of how artifcial intelligence could be aided to explore such systems for the prediction and directed design of the desired NM-protein interactions.